2.0 2012-05-31 13:59:06 -0600 2015-06-03 15:54:23 -0600 ECMDB03426 M2MDB000501 Pantetheine Pantetheine is the mercaptoethyl conjugated amide analogue of pantothenic acid (Vitamin B5). The dimer of this compound, pantethine is more commonly known, and is considered to be a more potent form of vitamin B5 than pantothenic acid. Pantetheine is an intermediate in the production of coenzyme A, an intermediate in the pathway of coenzyme A formation. (R)-Pantetheine D-Pantetheine Lactobacillus bulgaricus factor LBF Pantotheine C11H22N2O4S 278.368 278.130027892 2,4-dihydroxy-3,3-dimethyl-N-{2-[(2-sulfanylethyl)carbamoyl]ethyl}butanamide pantetheine 496-65-1 CC(C)(CO)C(O)C(=O)NCCC(=O)NCCS InChI=1S/C11H22N2O4S/c1-11(2,7-14)9(16)10(17)13-4-3-8(15)12-5-6-18/h9,14,16,18H,3-7H2,1-2H3,(H,12,15)(H,13,17) ZNXZGRMVNNHPCA-UHFFFAOYSA-N Solid Cytoplasm Periplasm logp -0.10 ALOGPS logs -2.83 ALOGPS solubility 4.08e-01 g/l ALOGPS logp -1.5 ChemAxon pka_strongest_acidic 10.07 ChemAxon pka_strongest_basic -1.5 ChemAxon iupac 2,4-dihydroxy-3,3-dimethyl-N-{2-[(2-sulfanylethyl)carbamoyl]ethyl}butanamide ChemAxon average_mass 278.368 ChemAxon mono_mass 278.130027892 ChemAxon smiles CC(C)(CO)C(O)C(=O)NCCC(=O)NCCS ChemAxon formula C11H22N2O4S ChemAxon inchi InChI=1S/C11H22N2O4S/c1-11(2,7-14)9(16)10(17)13-4-3-8(15)12-5-6-18/h9,14,16,18H,3-7H2,1-2H3,(H,12,15)(H,13,17) ChemAxon inchikey ZNXZGRMVNNHPCA-UHFFFAOYSA-N ChemAxon polar_surface_area 98.66 ChemAxon refractivity 70.7 ChemAxon polarizability 29.33 ChemAxon rotatable_bond_count 8 ChemAxon acceptor_count 4 ChemAxon donor_count 5 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Pantothenate and CoA biosynthesis The CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate. The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate. On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine. Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid. Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine. The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA. Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A. . The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase (EC 6.3.2.1, pantoate—β-alanine ligase (AMP-forming) followed by EC 2.7.1.33, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 2.7.1.169, pantoate kinase acts before EC 6.3.2.36, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III. The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC 2.7.1.24, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth. The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06]. PW000828 ec00770 Metabolic Specdb::CMs 11040 Specdb::CMs 38599 Specdb::CMs 152039 Specdb::NmrOneD 21842 Specdb::NmrOneD 21843 Specdb::NmrOneD 21844 Specdb::NmrOneD 21845 Specdb::NmrOneD 21846 Specdb::NmrOneD 21847 Specdb::NmrOneD 21848 Specdb::NmrOneD 21849 Specdb::NmrOneD 21850 Specdb::NmrOneD 21851 Specdb::NmrOneD 21852 Specdb::NmrOneD 21853 Specdb::NmrOneD 21854 Specdb::NmrOneD 21855 Specdb::NmrOneD 21856 Specdb::NmrOneD 21857 Specdb::NmrOneD 21858 Specdb::NmrOneD 21859 Specdb::NmrOneD 21860 Specdb::NmrOneD 21861 Specdb::MsMs 23357 Specdb::MsMs 23358 Specdb::MsMs 23359 Specdb::MsMs 30155 Specdb::MsMs 30156 Specdb::MsMs 30157 Specdb::MsMs 2381456 Specdb::MsMs 2381457 Specdb::MsMs 2381458 Specdb::MsMs 2580783 Specdb::MsMs 2580784 Specdb::MsMs 2580785 HMDB03426 479 466 C00831 16753 CPD-511 Pantetheine Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Mandel, Alexander L.; La Clair, James J.; Burkart, Michael D. Modular Synthesis of Pantetheine and Phosphopantetheine. Organic Letters (2004), 6(26), 4801-4803. Pantothenate kinase P0A6I3 COAA_ECOLI coaA http://ecmdb.ca/proteins/P0A6I3.xml Adenosine triphosphate + Pantetheine <> ADP + Pantetheine 4'-phosphate R02971 Pantetheine + Water + Pantetheine > Pantothenic acid + Cysteamine + Pantothenic acid PW_R002989 Pantetheine + Adenosine triphosphate + Pantetheine > Pantetheine 4'-phosphate + Adenosine diphosphate + pantotheine 4'-phosphate + ADP PW_R002992